Testosterone Perturbs Epidermal Permeability Barrier Homeostasis

Kao, Jack; Garg, Amit; Man, Mao‐Qiang; Crumrine, Debra; Ghadially, Ruby; Feingold, Kenneth R.; Elias, Peter M.

doi:10.1046/j.1523-1747.2001.01281.x

Cited by 63 publications

(47 citation statements)

References 53 publications

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“…Together with the findings of age-related changes in pH values, one could hypothesize that surface pH is modulated, at least in part, by a sexhormone-dependent feedback mechanism. In support of this hypothesis, recent studies have shown the influence of sex hormones on corneocyte structure and SC barrier function [84,85].…”

Section: Factors That Influence Human Surface Phmentioning

confidence: 87%

Stratum corneum pH: Formation and Function of the ‘Acid Mantle’

Fluhr¹,

Elias²

2002

Exog Dermatol

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169

112

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Although the acidic surface pH of the skin has been known for over a century, the stratum corneum (SC) pH gradient has been discovered only recently. After removal of SC layers with sequential tape strips, in humans, surface pH starts at 4.5–5.3, increasing by about 2–3 units until it reaches 6.8 in the lower SC. Both exogenous [free fatty acids (FFA) from sebaceous lipid, microbial metabolites, lactic acid from eccrine glands] and endogenous epidermal (enzymatic; membrane antiporters/pumps) mechanisms have been hypothesized to contribute to SC acidification. Three endogenous mechanisms have been identified to date that not only could influence SC pH, but also regulate one or more key SC functions: (1) the histidine-to-urocanic-acid pathway; (2) the phospholipid-to-FFA pathway, and (3) the sodium proton antiporter (NHE1). Additional factors that influence human surface pH have been detected. Endogenous factors, unrelated to pathological features, such as racial differences, topographical variation, gender differences, developmental and age-related changes have been reported. In contrast to adults, human newborn SC displays a near-neutral surface pH, which declines rapidly over the first postnatal month. Furthermore, endogenous factors have been described, as in atopic dermatitis, seborrheic dermatitis, diabetes, renal insufficiency and ichthyosis associated with an increased pH. Exogenous factors, like the use of detergents and cleansing products as well as SC hydration, can modify the surface pH. The consequences of SC acidification for several key SC functions are becoming clear, including (1) the role of an acidic pH for SC permeability barrier homeostasis, (2) the pH dependence of extracellular lipid processing and (3) SC integrity/cohesion. Integrity is defined as a measure of resistance to dissociation of adjacent corneocytes by tape stripping (cohesion is a related index defined as the amount of protein removed per stripping). (4) Proteolytic processes leading to desquamation are pH dependent, and (5) an acidic pH provides important antimicrobial resistance.

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Section: Factors That Influence Human Surface Phmentioning

confidence: 87%

Stratum corneum pH: Formation and Function of the ‘Acid Mantle’

Fluhr¹,

Elias²

2002

Exog Dermatol

Self Cite

169

112

View full text Add to dashboard Cite

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“…For CD quantitation, CD length, selected at random from the first and second cell layers of the lower SC, was measured. The ratio of the total length of intact CD to the total length of cornified envelopes was determined by planimetry, as described previously (21,24,30).…”

Section: Methodsmentioning

confidence: 99%

Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function

Choi¹,

Demerjian²,

Crumrine³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent studies have demonstrated that PS decreases epidermal proliferation and differentiation, impairs permeability barrier homeostasis, and decreases stratum corneum integrity. PS also increases the production of endogenous glucocorticoids (GC), and both systemic and topical GC cause adverse effects on epidermal structure and function similar to those observed with PS. We therefore hypothesized that increased endogenous GC in PS mediates its adverse cutaneous effects. To test this hypothesis, we used two independent approaches, administering either RU-486, a GC receptor antagonist that inhibits GC action, or antalarmin, a corticotropin-releasing hormone (CRH) receptor antagonist that prevents increased GC production in the face of PS. Inhibition of either GC action or production prevents the PS-induced decline in epidermal cell proliferation and differentiation, impairment in permeability barrier homeostasis, and decrease in stratum corneum (SC) integrity. Moreover, the pathophysiological basis for the abnormality in permeability barrier homeostasis; i.e., decreased lamellar body production and secretion, is restored toward normal by inhibition of GC action. Similarly, the mechanistic basis for the decrease in SC integrity, i.e., a reduction in corneodesmosomes, is also normalized by inhibition of GC action. Thus many of the adverse effects of PS on epidermal structure and function can be attributed to increased endogenous GC and conversely, approaches that either reduce GC production or action might benefit cutaneous disorders that are provoked or exacerbated by PS.RU-486; corticotropin-releasing hormone; stratum corneum integrity; barrier homeostasis PSYCHOLOGICAL STRESS (PS) is well recognized to provoke, exacerbate, or propagate many cutaneous dermatoses, including psoriasis and atopic dermatitis (20,31,35). Many of the disorders that are adversely affected by PS are also associated with abnormal permeability barrier function (17, 18). Studies in both rodents and human have demonstrated that PS perturbs permeability barrier homeostasis. While basal permeability barrier function is normal, the kinetics of barrier recovery following acute barrier disruption are delayed (2,7,8,16). This delay in barrier recovery is accounted for by a decrease in the production and secretion of lamellar bodies (LB) (5) with a resultant decrease in the formation of the extracellular lamellar membranes that mediate epidermal permeability barrier function (10). Epidermal lipid synthesis is essential for providing the lipids required for the formation of LB (11). Accordingly, the decrease in LB secretion in PS animals is explained by a decrease in epidermal lipid synthesis (5). Of note, the abnormality in barrier homeostasis induced by PS can be normalized by the topical applications of a mixture of barrier lipids, which normalize LB formation and secretion (5).In addition to adversely effecting barrier homeostasis, PS also decreases keratinocyte proliferation, impairs epidermal differentiation, and decreases stratum corneum (SC) ...

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“…However, the impact of class-I ligands in postnatal skin is less well understood. Similar to in utero, highnormal to supranormal levels of androgens provoke a decline in permeability barrier homeostasis in adult murine and human skin [16]. Yet, in contrast to in utero, increases in endogenous glucocorticoids, induced by psychological stress, as well as systemic administration of supraphysiologic levels of exogenous steroids, delay barrier recovery rates after acute perturbations [17].…”

Section: Endogenous Ligands Of Nuclear Hormone Receptorsmentioning

confidence: 99%